Abstract

Background

Ligands of peroxisome proliferator–activated receptor alpha (PPAR–α) have been shown to reduce ischaemia/reperfusion injury. The mechanisms behind this effect are not well known. We hypothesized that activation of PPAR–α exerts cardioprotection via a mechanism related to nitric oxide (NO) and endothelin–1 (ET–1).

Results

There were no haemodynamic differences between the groups during the experiment. The IS was 78 ± 3% of the area at risk in the DMSO group and 77 ± 2% in the NaCl group (P = NS). WY reduced IS to 56 ± 3% (P < 0.001 vs. DMSO group). When WY was administered in combination with L–NNA the cardioprotective effect was abolished (IS 73 ± 3%, P < 0.01 vs. WY 14643). L–NNA did not affect IS per se (78 ± 2%, P = NS). The expression of eNOS but not iNOS protein in ischaemic myocardium from rats was increased in the group given WY (P < 0.05). ET–1 mRNA levels were lower in the ischaemic myocardium following WY administration.

Conclusion

The results suggest that the PPAR–α activation protects the rat myocardium against ischaemia/ reperfusion injury via a mechanism related to production of NO, and possibly ET–1.

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